Automated High Content Confocal Imaging of Organ-Chips

Microphysiological systems are in vitro models that aim to accurately recapitulate the organ microenvironment by including additional physiological cues such as shear stress from the microfluidic component. Implementation of microphysiological systems within the pharmaceutical industry aims to improve the probability of success of drugs by generating models that are human and disease relevant. AstraZeneca in collaboration with Emulate has invested in the use of ‘organs-on-chips’ for pre-clinical efficacy and toxicity prediction. Whilst capturing cellular phenotype via imaging in response to drug exposure is a useful readout in these models, application has been limited due to difficulties in the ability to image the chips robustly and at scale.
We designed and 3D printed bespoke adaptors to allow compatibility of such chips with a high throughput, high content confocal microscope (Yokogawa CV7000). We also implemented a workflow that incorporates intelligent scanning to map out the cell chambers within each chip ready for higher magnification imaging. At the higher resolution, Z stack slices through the different cell layers within each chip are captured. The process from mapping of the chip regions to higher resolution Z stacking of the cells within each chip is fully automated. By automating this process, we have reduced acquisition time from >16 hours per 8 chips (manual) to just 50 mins (95% time saving), as well as reducing variability, improving quality, and removing user bias. Furthermore, it is now possible to examine whether cells show differential responses depending upon their location on the chip.
The setup of this automated workflow will be described along with application to a multi-cellular, liver Organ-Chip system where detailed cellular phenotype (including morphology, proliferation, apoptosis, and mitochondrial function) in response to a proprietary AstraZeneca compound exposure was captured.

Samantha Peel

Associate Principal ScientistAstraZeneca

Samantha Peel is an Associate Principal Scientist currently working within the High Content Biology team at AstraZeneca. Her current role is to develop phenotypic cell & tissue based imaging assays for target identification as well as the prediction of efficacy and safety in early drug discovery. Before joining AstraZeneca in 2010, Samantha held a postdoctoral research position at the University of Nottingham where her work focussed on cell signalling in airway smooth muscle. Samantha holds a PhD in cell signalling from the University of Nottingham and a BSc in Pharmacology from the University of Bath.